| 1. |
- Petrova, Tatiana V, et al.
(author)
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Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor.
- 2002
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In: EMBO Journal. - 0261-4189 .- 1460-2075. ; 21:17
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Journal article (peer-reviewed)abstract
- Lymphatic vessels are essential for fluid homeostasis, immune surveillance and fat adsorption, and also serve as a major route for tumor metastasis in many types of cancer. We found that isolated human primary lymphatic and blood vascular endothelial cells (LECs and BECs, respectively) show interesting differences in gene expression relevant for their distinct functions in vivo. Although these phenotypes are stable in vitro and in vivo, overexpression of the homeobox transcription factor Prox-1 in the BECs was capable of inducing LEC-specific gene transcription in the BECs, and, surprisingly, Prox-1 suppressed the expression of approximately 40% of the BEC-specific genes. Prox-1 did not have global effects on the expression of LEC-specific genes in other cell types, except that it up-regulated cyclin E1 and E2 mRNAs and activated the cyclin e promoter in various cell types. These data suggest that Prox-1 acts as a cell proliferation inducer and a fate determination factor for the LECs. Furthermore, the data provide insights into the phenotypic diversity of endothelial cells and into the possibility of transcriptional reprogramming of differentiated endothelial cells.
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| 2. |
- Solovieva, Svetlana, et al.
(author)
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Interleukin 1 polymorphisms and intervertebral disc degeneration
- 2004
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In: Epidemiology. - : Ovid Technologies (Wolters Kluwer Health). - 1044-3983 .- 1531-5487. ; 15:5, s. 626-33
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Journal article (peer-reviewed)abstract
- BACKGROUND: Enzymatic breakdown of the extracellular matrix, and possibly local inflammation, contributes to intervertebral disc degeneration. We investigated whether polymorphisms within the IL-1 gene locus are associated with lumbar disc degeneration and whether the effect of occupational physical load on disc degeneration is modified by the polymorphisms. METHODS: Genotypes were determined from 133 middle-aged men who underwent magnetic resonance imaging of the lumbar spine. The participants represented 3 occupations: 40 were machine drivers, 42 carpenters, and 51 office workers. We evaluated decreased signal intensity of the nucleus pulposus, disc bulges, and decreased disc height as signs of degeneration in the L2/L3-L5/S1 discs. RESULTS: The odds ratio for disc bulges was 2.4 (95% confidence interval = 1.2-4.8) and 1.9 (1.0-3.7), in carriers of the IL-1alphaT or IL-1betaT alleles, respectively. The TT genotype of the IL-1alpha gene carried more than 3-fold risk of disc bulges as compared with the CC genotype. CONCLUSIONS: IL-1 gene cluster polymorphisms could affect the risk of disc degeneration. The effect of physical workload seems to be modified by the IL-1 gene polymorphisms.
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